Earlier the investigators determined the safety and feasibility of tumor lysate-pulsed dendritic cells as therapeutic adjuvants in mesothelioma patients. Because pre-clinical data in mice had shown that better results were obtained when regulatory T cells were depleted using low-dosis of cyclophosphamide, ten patients who responded on chemotherapy are selected for DC-treatment in combination with Endoxan.

Patients with mesothelioma who are fit enough to be treated with chemotherapy and enough tumor material was available are asked for participation in this study. After 4 cycles of Alimta chemotherapy, a leukapheresis is performed of which the monocytes are used for differentiation to DCs using different cytokines. The procedure to grow DCs in vitro and pulse them with tumor lysate is performed according to our earlier performed phase I study that was approved by our local ethics committee. Three doses of properly pulsed autologous DCs (MesoCancerVac) are then re-injected every two weeks. Patients will be treated with a low dose of CTX for seven day in a row the week before the 1st vaccination, the weeks in between the 2nd, and for one week after the 3rd vaccination.

Biological: DC + CTX

3x 50x10e6 DC + cyclophosphamide

Other Name: Endoxan

Detailed Description:

Currently there is no satisfactory low-toxicity treatment for patients with mesothelioma (MM). Based on studies in other types of cancer in humans where beneficial effects were obtained, and based on our pre-clinical data in a mouse model for MM, led to the introduction of DC-immunotherapy for human MM in 2005. A beneficial effect of immunotherapy in MM patients without major side effects was found, however, research has shown that DC immunotherapy might be further improved. The objectives of the here proposed phase study are:

To define the safety and toxicity of low dose CTX in combination with MesoCancerVac in patients with MM.

To determine if vaccination with low dose CTX in combination with MesoCancerVac results in a detectable immune response by skin DTH reactions on MM crude antigen and KLH and by in vitro laboratory analysis.

To observe and document anti-cancer activity by laboratory evaluation (e.g. decrease in Tregs, increase in CTLs using 51Cr release and IFN-gamma ELISPOT)

Ability to return to the Erasmus MC for adequate follow-up as required by this protocol.

Able to tolerate oral therapy

No impairment of gastrointestinal (GI) function or GI disease that may affect or alter absorption of CTX (e.g., mal-absorption syndrome, history of total gastrectomy/significant small bowel resection)

No history of allergic reactions (≥ grade 3 or 4) to compounds of similar chemical or biologic composition to CTX (i.e., alkylating agents)

No known intolerance or hypersensitivity reaction to CTX

Exclusion criteria:

Conditions that make the patient unfit for chemotherapy or progressive disease after 4 cycles of chemotherapy.

Pleurodesis at the affected side before the pleural fluid is obtained.

Medical or psychological impediment to probable compliance with the protocol.

Patients on steroid (or other immunosuppressive agents) are excluded on the basis of potential immune suppression. Patients must have had 6 weeks of discontinuation and must stop of any such treatment during the time of the study.

No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, superficial or in-situ cancer of the bladder or other cancer for which the patient has been disease-free for five years.

Serious concomitant disease, no active infections. Patients with a history of autoimmune disease or organ allografts, or with active acute or chronic infection, including HIV (as determined by ELISA and confirmed by Western Blot) and viral hepatitis (as determined by HBsAg and Hepatitis C serology).

Patients with serious intercurrent chronic or acute illness such as pulmonary (asthma or COPD) or cardiac (NYHA class III or IV) or hepatic disease or other illness considered by the study coordinator to constitute an unwarranted high risk for investigational DC treatment.

An organic brain syndrome or other significant psychiatric abnormality which would comprise the ability to give informed consent, and preclude participation in the full protocol and follow-up.

Absence of assurance of compliance with the protocol. Lack of availability for follow-up assessment.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01241682